The purpose of this study was to clarify the expression of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier (BBB). DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597 fmol/μg protein, respectively, as determined by a quantitative targeted absolute proteomics technique. Using an antibody-free method established by Kubo et al. (2015), we found that SLC5A6 was preferentially localized at the luminal membrane of brain capillary endothelium. Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [(3) H]biotin and [(3) H]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line hCMEC/D3. SLC5A6-mediated transport in hCMEC/D3 was markedly inhibited not only by biotin and pantothenic acid, but also by prostaglandin E2, lipoic acid, docosahexaenoic acid, indomethacin, ketoprofen, diclofenac, ibuprofen, phenylbutazone and flurbiprofen. This study is the first to confirm expression of SLC5A6 in human brain microvessels and to provide evidence that SLC5A6 is a major contributor to luminal uptake of biotin and pantothenic acid at the human BBB. This article is protected by copyright. All rights reserved.

Drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate
pharmacological action can be advantageously formulated as orally fast-disintegrating
tablets (FDTs or ODTs). Therefore, taste masking of active ingredients becomes essential
in these systems because the drug is entirely released in the mouth. Despite advances
in the FDT technologies, formulation of drugs with a bitter taste is still a challenge,
especially when the amount of drug is high. In this study, a new solution is being
developed to incorporate higher doses of a model bitter taste drug; ketoprofen, without
affecting the fast-disintegrating properties of the formulation. The unpleasant taste
of the active drug usually masked by adding flavoring ingredients and sweeteners to
improve taste and palatability but in this study a novel approach of using a polymer;
Eudragit EPO and a granulation procedure of this polymer with the active drug was
applied to mask the bitter taste of ketoprofen. In order to produce ketoprofen FDT
formulations, a two-stepped procedure was followed; granulation process with the taste-masking
agent (Eudragit EPO) and then direct compression (F3 and F4). In F1 and F2 formulations,
granulation process was not implemented in order to observe the effect of application
method of Eudragit EPO. As well as observing the effect of taste-masking agent, crospovidone
and sodium starch glycolate were used in different concentrations (2, 4 and 8wt%)
to examine the influence of superdisintegrants on FDT properties. All the FDTs containing
30 mg ketoprofen (F1, F2, F3 and F4) were evaluated by means of in vitro quality control
tests.

A new dendrimer-functionalized mesoporous silica material based on large-pore 3D cubic
Korea Advanced Institute of Science and Technology-6 (KIT-6) was synthesized by the
growing of dendritic branches inside the mesopores of aminopropyl functionalized KIT-6.
Detailed physical characterizations using transmission electron microscopy, nitrogen
adsorption-desorption measurements, Fourier transform infrared (FTIR) spectroscopy,
and elemental analysis reveal that the multifunctional dendrimers have been grown
successfully within the confined spaces of mesopores. Although the 3D ordered mesoporous
architecture of KIT-6 was well preserved, there was a significant and continuous decrease
in pore size, specific surface area (SBET) and pore volume when increasing dendrimer
generation up to six. In order to get a compromise between the SBET, pore size and
density of functionalities, the dendrimer-functionalized KIT-6 (DF-KIT-6) for generation
2 (SBET, 314.2m(2)g(-1); pore size, 7.9nm; carbon and nitrogen contents, 19.80% and
1.92%) was selected for solid phase extraction (SPE) applications. The DF-KIT-6 was
then evaluated as a reversed-phase/anion-exchange mixed-mode sorbent for extraction
of the selected acidic drugs (ketoprofen, KEP; naproxen, NAP; and ibuprofen, IBU),
since the dendrimers contained both hydrocarbonaceous and amine functionalities. The
effective parameters on extraction efficiency such as sample pH and volume, type and
volume of eluent and wash solvents were optimized. Under the optimized experimental
conditions, the DF-KIT-6 based SPE coupled with HPLC-UV method demonstrated good sensitivity
(0.4-4.6ngmL(-1) detection of limits) and linearity (R(2)>0.990 for 10-2000ngmL(-1)
of KEP and IBU, and 1-200ngmL(-1) of NAP). The potential use of DF-KIT-6 sorbent for
preconcentration and cleanup of acid drugs in human urine samples was also demonstrated.
Satisfactory recoveries at two spiking levels (30 and 300ngmL(-1) for KEP and IBU,
3 and 30ngmL(-1) for NAP) were obtained in the range of 85.7-113.9% with RSD values
below 9.3% (n=3).

This prospective randomized blinded clinical study aimed to investigate the potential
of vedaprofen for preventive analgesia, comparing its analgesic effects with ketoprofen
administered post-operatively in dogs undergoing maxillectomy or mandibulectomy.Pain control was effective and rescue analgesia was not necessary in any group. Pain scores were not significantly different between groups. The respiratory rate and rectal temperature were decreased in all groups at extubation until 6 hours post-extubation compared to baseline. Cortisol and epinephrine levels were increased only at 0.5 hours after extubation in all groups compared to baseline.Vedaprofen did not present any preventive analgesic effect. Pre- and postoperative
vedaprofen were as effective as ketoprofen for postoperative pain control.

The aim of this study was to test the cytostatic potential of ketoprofen in the in
vitro treatment of cells derived from colon and cervix cancer.NF-κB and cyclooxygenase can have a role in different stages of the development and
progression of cancer. In recent years, special attention has been paid to the possible
cytostatic potential of nonsteroidal anti-inflammatory drugs. There are no published
data on the use of ketoprofen in pharmacotherapy of the colon and cervical carcinoma.We examined the effect of ketoprofen alone or in combination with cisplatin and 5-fluorouracil
on proliferation of the two cell lines, HeLa (human cervical carcinoma cells) and
Caco-2 (human colon cancer cells) by MTT test. Measurement of the level of NF-κB was
also performed in the cells of both cell lines.The results of present study have shown that at least one of the mechanisms of antiproliferating
and/or cytostatic effects of different concentrations of ketoprofen on Caco-2 and
HeLa cells could include the transcription factor NF-κB.Since this transcription factor is controlled by the altered expression of COX-2,
the inhibition of this enzyme by ketoprofen may represent a significant step in synergistic
cascade of the therapy and prevention of colon and cervical cancer (Tab. 4, Ref. 31).

The goal of this work was to combine the ketoprofen anti-inflammatory effect with the ascorbic acid antioxidant properties for a more efficient treatment of colonic pathologies. With this aim, microspheres (MS) based on both waxy materials (ceresine, Precirol(®) and Compritol(®)) or hydrophilic biopolymers (pectine, alginate and chitosan) loaded with the two drugs were developed, physicochemically characterized and compared in terms of entrapment efficiency, in vitro release profiles, potential toxicity and drug permeation properties across the Caco-2 cell line. Waxy MS revealed an high encapsulation efficiency of ketoprofen but a not detectable entrapment of ascorbic acid, while polymeric MS showed a good entrapment efficiency of both drugs. All MS need a gastro-resistant coating, to avoid any premature release of the drugs. Ketoprofen release rate from polymeric matrices was clearly higher than from the waxy ones. In contrast, the ASC release rate was higher, due to its high hydro-solubility. Cytotoxicity studies revealed the safety of all the formulations. Transport studies showed that the ketoprofen apparent permeability increased, when formulated with the different MS. In conclusion, only polymeric MS enabled an efficient double encapsulation of both the hydrophilic and lipophilic drugs, and, in addition, presented higher drug release rate and stronger enhancer properties.

Human serum albumin (HSA), transporting protein, is exposed during its life to numerous
factors that cause its functions become impaired. One of the basic factors - glycation
of HSA - occurs in diabetes and may affect HSA-drug binding. Accumulation of advanced
glycation end-products (AGEs) leads to diseases e.g. diabetic and non-diabetic cardiovascular
diseases, Alzheimer disease, renal disfunction and in normal aging. The aim of the
present work was to estimate how non-enzymatic glycation of human serum albumin altered
its tertiary structure using fluorescence technique. We compared glycated human serum
albumin by glucose (gHSAGLC) with HSA glycated by fructose (gHSAFRC). We focused on
presenting the differences between gHSAFRC and nonglycated (HSA) albumin used acrylamide
(Ac), potassium iodide (KI) and 2-(p-toluidino)naphthalene-6-sulfonic acid (TNS).
Changes of the microenvironment around the tryptophan residue (Trp-214) of non-glycated
and glycated proteins was investigated by the red-edge excitation shift method. Effect
of glycation on ligand binding was examined by the binding of phenylbutazone (PHB)
and ketoprofen (KP), which a primary high affinity binding site in serum albumin is
subdomain IIA and IIIA, respectively. At an excitation and an emission wavelength
of λex 335nm and λem 420nm, respectively the increase of fluorescence intensity and
the blue-shift of maximum fluorescence was observed. It indicates that the glycation
products decreases the polarity microenvironment around the fluorophores. Analysis
of red-edge excitation shift method showed that the red-shift for gHSAFRC is higher
than for HSA. Non-enzymatic glycation also caused, that the Trp residue of gHSAFRC
becomes less accessible for the negatively charged quencher (I(-)), KSV value is smaller
for gHSAFRC than for HSA. TNS fluorescent measurement demonstrated the decrease of
hydrophobicity in the glycated albumin. KSV constants for gHSA-PHB systems are higher
than for the unmodified serum albumin, while KSV values for gHSA-KP systems are only
slightly lower than that obtained for HSA-KP. The affinity of PHB to the glycated
HSA is stronger than to the non-glycated in the first class binding sites within subdomain
IIA, in the vicinity of Trp-214. Ketoprofen bound to unmodified human serum albumin
stronger than for glycated albumin and one class of binding sites is observed (Scatchard
linear plots).

Intramolecular hydrogen abstraction reactions among ketoprofen (KP) and purine nucleoside
dyads have been proposed to form ketyl-sugar biradical intermediates in acetonitrile.
Femtosecond transient absorption studies on KP and purine nucleoside dyads reveal
that the triplet state of the KP moiety of the dyads with cisoid structure decay faster
(due to an intramolecular hydrogen abstraction reaction to produce a ketyl-sugar biradical
intermediate) than the triplet state of the KP moiety of the dyads with transoid structure
detected in acetonitrile solvent. For the cisoid 5-KP-dG dyad, the triplet state of
the KP moiety decays too fast to be observed by ns-TR(3); only the ketyl-sugar biradical
intermediates are detected by ns-TR(3) in acetonitrile. For the cisoid 5-KP-dA dyad,
the triplet states of the KP moiety could be observed at early nanosecond delay times,
and then it quickly undergoes intramolecular hydrogen abstraction to produce a ketyl-sugar
biradical intermediate. For the cisoid 5-KPGly-dA and transoid 3-KP-dA dyads, the
triplet state of the KP moiety had a longer lifetime due to the long distance chain
between the KP moiety and the purine nucleoside (5-KPGly-dA) and the transoid structure
(3-KP-dA). The experimental and computational results suggest that the ketyl-sugar
biradical intermediate is generated with a higher efficiency for the cisoid dyad.
However, the transoid dyad exhibits similar photochemistry behavior as the KP molecule,
and no ketyl-sugar biradical intermediate was observed in the ns-TR(3) experiments
for the transoid 3-KP-dA dyad.

Fabric phase sorptive extraction (FPSE) is a new, yet very promising member of the sorbent-based sorptive microextraction family. It has simultaneously improved both the extraction sensitivity and the speed of the extraction by incorporating high volume of sol-gel hybrid inorganic-organic sorbents into permeable fabric substrates. The advantages of FPSE have been investigated for the determination of four non-steroidal anti-inflammatory drugs, ibuprofen, naproxen, ketoprofen and diclofenac, in environmental water samples in combination with gas chromatography-mass spectrometry. Initially, the significance of several parameters affecting FPSE: sorbent chemistry, matrix pH and ionic strength were investigated using a mixed level factorial design (3(1)×2(2)). Then, other important parameters e.g., sample volume, extraction kinetics, desorption time and volume were also carefully studied and optimized. Due to the high sorbent loading on the FPSE substrate in the form of ultra-thin coating and the open geometry of the microextraction device, higher mass transfer of the target analytes occurs at a faster rate, leading to high enrichment factors in a relatively short period of time (equilibrium times: 45-100min). Under optimal operational conditions, the limits of detection (S/N=3) were found to be in the range of 0.8ngL(-1) to 5ngL(-1). The enrichment factors ranged from 162 to 418 with absolute extraction efficiencies varied from 27 to 70%, and a good trueness (82-116% relative recoveries) indicating that the proposed method can be readily deployed to routine environmental pollution monitoring. The proposed method was successfully applied to the analysis of target analytes in two influent and effluent samples from a wastewater treatment plant and two river water samples in Spain.

Cinchona alkaloids (quinine, quinidine, cinchonine, cinchonidine) alkylated at N(1)
with chloromethyl anthracene can serve as fluorescent sensors for chiral carboxylic
acids. These cinchona ammonium salts are shown to bind chiral carboxylic acids while
displaying an increase in fluorescence intensity that can be utilized in determination
of enantiomeric excess (ee). Sensor arrays composed of four cinchona ammonium salts
are used for quantitative analysis of ee in several non-steroidal anti-inflammatory
drugs (NSAIDs), such as enantiomers of ibuprofen, ketoprofen, and naproxen.